(Adapted from the Applicant's Abstract) This SCOR entitled "Genes Involved in Cardiac Development" consists of six projects and one Core Laboratory. The themes of this SCOR relate to the identification, characterization and function of genes that relate to cardiac development. These projects and the core laboratory are integrated in their efforts and directed by investigators who have appointments in the Departments of Anatomy and Cell Biology, Biochemistry, Biological Sciences, Pediatrics (Cardiology and Genetics), Physiology and Biophysics and Preventive Medicine and Environmental Health. The SCOR program does not try to address all of the basic and clinical issues related to congenital heart disease. The major focus and rationale for the SCOR Program is as follows: There exists a genetic susceptibility to atrial septal, ventricular septal and AV canal defects. The genes that are involved in the formation of these septal areas of the heart will be identified from temporal and spatial studies of rodent embryos and will become candidates for further investigation in this SCOR. Project 1, a human study, will recruit and examine probands with these three cardiac malformations and their family members. The DNA from these subjects will be used to carry out linkage and association studies of candidate genetic regions using STRP markers characterized in individual as well as pooled DNA samples. Project 2 along with the In Situ Core Laboratory will identify genes that are spatially and/or temporally regulated during heart development. Project 3 will evaluate the role of differentially expressed genes in cardiac morphogenesis that relate to the three defects as well as other congenital malformations. Project 4 will study the role of dystroglycan which is expressed throughout the embryonic heart during development. Project 5 will focus on the spatial-temporal regulation of coronary vasculogenesis and angiogenesis which is necessary for myocardial and septal development. Project 6 will develop vectors to allow investigation of spatial and temporal expression of genes involved in septal and other morphologic areas during early cardiac development. In Situ Core Laboratory will localize temporal and spatial patterns of expressions of selected clones for Projects 3, 4, 5, and 6. These efforts have great potential to identify genes that are risk factors for the development of frequently occurring cardiac birth defects and thus have the additional potential of developing preventive measures.